AB0846 HLA-B51 prevalence in patients with spondyloarthritis and impact on disease phenotype: a case-control study
Authors: N. Ziade, R. Nacouzi, K. Mroue’, G. Merheb, P. Ghorra
Journal: Annals of the Rheumatic Diseases (2022)

Background Spondyloarthritis (SpA) is a group of rheumatic diseases with a heritable component associated with Human Leucocyte Antigen B27 (HLA-B27). Although many studies have reported an overlap between the clinical features of SpA and Behcet’s disease (BD), as well as an increased prevalence of HLA-B27 in BD, the prevalence of HLA-B5 (namely B51 and B52, the split antigens of B5) in SpA, have been scarcely examined, particularly in countries with a low HLA-B27 prevalence. Objectives To estimate the prevalence of HLA-B51 and HLA-B52 in patients with SpA compared to healthy controls (HC), to identify the alleles found in HLA-B locus in patients with SpA compared to HC, and to evaluate the impact of HLA-B51 on SpA disease phenotype. Methods A case-control study included consecutive patients with a diagnosis of SpA (axial SpA (axSpA), peripheral SpA (pSpA), and psoriatic arthritis (PsA)) from three rheumatology clinics. HC were recruited among blood donors and medical students. Demographic data, as well as SpA and BD disease features, were collected through an interview with a trained medical student and file review (low back pain, peripheral joint disease, enthesitis, dactylitis, psoriasis, uveitis, inflammatory bowel disease, family history, oral and genital ulcerations, skin, vascular and neurologic manifestations, CRP, BASDAI, imaging of the spine and sacroiliac joints). The entire B locus was tested using molecular biology technique on Luminex with the possibility of precise B51/B52 differentiation. The prevalence of HLA-B51/B52 was calculated in patients and compared to HC using the Chi-square test. A complete HLA-B mapping was performed for patients and HC. A binary logistic regression identified factors associated with HLA-B51 in patients with axSpA. Results Data from 119 HC and 89 patients with SpA were available (66 axSpA, 16 pSpA, and 7 PsA). Mean age of the patients was 44.8 years [SD 13.5], 66.3% were males, disease duration was 12 years [SD 12.7], 72.4% had a history of elevated CRP, 30.3% were positive for HLA-B27, 53.9% had sacroiliitis on MRI, 47.2% had radiographic sacroiliitis, and 23.6% had syndesmophytes. Oral ulcerations were reported in 38.2% of patients, genital ulcerations in 3.4%, uveitis in 5.6%, skin lesions in 18%, and vascular lesions in 3.4%. Patients with SpA fulfilled the classification criteria for BD in 2.9% (International Study Group criteria for BD) and 38.2% (International Criteria for BD). HLA-B51/B52 were found more frequently in patients with SpA (20.2%/ 7.9%) compared to HC (11.8%/4.2%), although the difference was not statistically significant. The difference was mainly driven by ant association between HLA-B51 and axSpA (27.2% versus 11.8%, OR 2.8 [95%CI 1.3-6.1], p=0.008) (Table 1). The most frequent allele in SpA and HC was HLA-B35; complete HLA-B mapping is shown in Figure 1. In patients with axSpA, HLA-B51 was associated with radiographic damage in peripheral joints, while it was negatively associated with sacroiliitis. Uveitis was numerically associated with HLA-B51, but the association did not reach statistical significance. Table 1. Prevalence of HLA-B5 genes in patients with spondyloarthritis (SpA) and healthy controls Controls SpA Axial SpA Peripheral SpA Psoriatic Arthritis p-value (SpA vs. Controls) p-value (axSpA vs controls) N 119 89 66 16 7 HLA-B51+, N (%) 14 (11.8) 18 (20.2) 18 (27.3) 0 (0.0) 0 (0.0) 0.094 0.008 HLA-B52+, N (%) 5 (4.2) 7 (7.9) 5 (7.6) 2 (12.5) 0 (0.0) 0.262 0.331 HLA-B51 or HLA-B52+, N (%) 19 (16) 21 (23.6) 19 (28.8) 2 (12.5) 0 (0.0) 0.167 0.039 Figure 1. Distribution of the HLA-B alleles in patients with spondyloarthritis and healthy controls (Statistically significant differences between patients and controls indicated with*) Conclusion HLA-B51/B52 were more numerically more prevalent in patients with SpA compared to HC. A statistically significant association was found between HLA-B51 and axSpA and correlated with more peripheral and less axial radiographic involvement. Acknowledgements The authors would like to thank the Research Council of Saint-Joseph University and NewBridge Pharmaceuticals FZ LLC for an unrestricted research grant to fund the study. Disclosure of Interests Nelly Ziade Speakers bureau: Roche, Abbvie, Eli Lilly, Pfizer, Janssen, Novartis, Pierre Fabre, Apotex, Pharmaline, Paid instructor for: Abbvie, Eli Lilly, Sanofi-Aventis, Pfizer, Janssen, Novartis, Grant/research support from: NewBridge Pharmaceutical FZ LLC (current study), Pfizer, Abbvie, Celgene, Rhea Nacouzi: None declared, Kamel Mroue’ Speakers bureau: Roche, Abbvie, Eli Lilly, Pfizer, Janssen, Novartis, Georges Merheb Speakers bureau: Roche, Abbvie, Eli Lilly, Pfizer, Janssen, Novartis, Pierre Ghorra: None declared